équipe EL FAR Oussama


Voltage-gated calcium channels provide the calcium influx that couples neuronal action potentials to the release of neurotransmitters contained in synaptic vesicles. The team’s project focuses on the use of molecular probes to elucidate the structure and distribution of calcium channels and the synaptic SNARE proteins (syntaxin I, SNAP-25, synaptobrevin / VAMP2) involved in exocytosis. It invoves dissecting the role of these proteins in neurotransmission and in certain neurological diseases and includes the following projects :

  • Regulation by cytoplasmic calcium sensors (synaptotagmins, calmodulin) of SNARE complex assembly and membrane fusion ;

  • Role of interactions between the SNARE complex, synaptophysin and V-ATPase in forming the fusion pore ;

  • Role of a polyglutamine expansion in the calcium channel Cav2.1 in the pathogenesis of type 6 spinocerebellar ataxia ;

  • Autoantibody assays for the diagnosis of autoimmune channelopathies ;

  • Quantification of synaptic proteins for the diagnosis of neuroendocrine markers in tumors ;

  • Development of novel in vitro assays for botulinum and tetanus neurotoxins

  • Main Publications :

    Ca2+-dependent regulation of synaptic complex assembly via a calmodulin and phospholipid binding domain of synaptobrevin
    Quetglas S, Leveque C, Miquelis R, Sato K, Seagar M.
    Proc. Natl. Acad. Sci USA 2000, 97 : 9695-9700

    Phoneutria nigriventer omega-phonetoxin IIA blocks the Cav2 family of calcium channels and interacts with omega-conotoxin-binding sites
    Gouvea dos Santos RG., Van Renterghem C., Martin-Moutot N., Mansuelle P., Cordeiro M., Diniz C.R., Mori Y., De Lima M.E. Seagar M.
    J. Biol. Chem., 2002, 277 : 13856-13862

    Calmodulin and lipid binding to synaptobrevin regulates calcium-dependent exocytosis
    Quetglas S., Iborra C., Sasakawa N., De Haro, L., Kumakura K., Sato K., Leveque C., Seagar M.
    EMBO J. 2002, 21 : 3970-3979

    Ca2+ / calmodulin transfers the membrane-proximal lipid-binding domain of the v-snare synaptobrevin from cis to trans bilayers
    De Haro L, Ferracci G, Opi S, Iborra C, Quetglass S, Miquelis R, Levêque C, Seagar M.
    Proc. Natl. Acad. Sci USA 2004,101 : 1578-1583

    Phoneutria nigriventer toxin 1 : a novel state-dependent inhibitor of neuronal sodium channels which interacts with ? conotoxin binding sites
    Martin-Moutot N, Mansuelle P, Alcaraz G, Gouvêa Dos Santos R, Cordeiro MN, De Lima ME, Seagar M, Van Renterghem C.
    Mol Pharmacol. 2006, 69 : 1931-1937

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